ARHGEF4

ARHGEF4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2DX1, 2PZ1, 3NMX, 3NMZ
Identifiers
Aliases	ARHGEF4, ASEF, ASEF1, GEF4, STM6, Rho guanine nucleotide exchange factor 4, SMIM39
External IDs	OMIM: 605216 MGI: 2442507 HomoloGene: 49414 GeneCards: ARHGEF4
Gene location (Human)
Chr.	Chromosome 2 (human)[1]
End	131,047,263 bp[1]
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)[2]
End	34,813,309 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• Rac guanyl-nucleotide exchange factor activity; • GO:0001948 protein binding; • protein domain specific binding; • guanyl-nucleotide exchange factor activity; • Rho guanyl-nucleotide exchange factor activity;
Cellular component	• cytoplasm; • ruffle membrane; • cytosol; • cell membrane; • cell projection; • membrane;
Biological process	• filopodium assembly; • regulation of Rho protein signal transduction; • GO:0007243 intracellular signal transduction; • regulation of small GTPase mediated signal transduction; • lamellipodium assembly; • positive regulation of apoptotic process; • G-protein coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	50649
	226970
	ENSG00000136002
	ENSMUSG00000037509
	Q9NR80
	Q7TNR9
NM_015320; NM_032995; NM_001367493; NM_001375900; NM_001375901;
	NM_001375902; NM_001375903; NM_001375904
	NM_183019; NM_001368773
NP_056135; NP_001354422; NP_001362829; NP_001362830; NP_001362831;
	NP_001362832; NP_001362833
	NP_898840; NP_001355702
	Wikidata
View/Edit Human	View/Edit Mouse

Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.[5][6]

Function

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. This protein is similar to rat collybistin protein. Alternative splicing of this gene generates two transcript variants that encode different isoforms. Also, there is possibility for the usage of multiple polyadenylation sites for this gene.[6]

Model organisms

*Arhgef4* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal[7]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal[8]
Peripheral blood lymphocytes	Abnormal[9]
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of ARHGEF4 function. A conditional knockout mouse line, called Arhgef4^{tm1a(KOMP)Wtsi}[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males has atypical peripheral blood lymphocyte parameters, including a decreased B cell number and an increased granulocyte number.[12]

Interactions

ARHGEF4 has been shown to interact with APC.[20]

References

GRCh38: Ensembl release 89: ENSG00000136002 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000037509 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Thiesen S, Kübart S, Ropers HH, Nothwang HG (Jul 2000). "Isolation of two novel human RhoGEFs, ARHGEF3 and ARHGEF4, in 3p13-21 and 2q22". Biochem Biophys Res Commun. 273 (1): 364–9. doi:10.1006/bbrc.2000.2925. PMID 10873612.
"Entrez Gene: ARHGEF4 Rho guanine nucleotide exchange factor (GEF) 4".
"Dysmorphology data for Arhgef4". Wellcome Trust Sanger Institute.
"Haematology data for Arhgef4". Wellcome Trust Sanger Institute.
"Peripheral blood lymphocytes data for Arhgef4". Wellcome Trust Sanger Institute.
"Salmonella infection data for Arhgef4". Wellcome Trust Sanger Institute.
"Citrobacter infection data for Arhgef4". Wellcome Trust Sanger Institute.
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
Mouse Resources Portal, Wellcome Trust Sanger Institute.
"International Knockout Mouse Consortium".
"Mouse Genome Informatics".
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y, Higuchi O, Akiyama T (2000). "Asef, a link between the tumor suppressor APC and G-protein signaling". Science. 289 (5482): 1194–7. doi:10.1126/science.289.5482.1194. PMID 10947987.

External links

Human ARHGEF4 genome location and ARHGEF4 gene details page in the UCSC Genome Browser.